The Complexities of Evaluating the Exposome in Psychiatry: A Data-Driven Illustration of Challenges and Some Propositions for Amendments

Gülöksüz, Sinan; Rutten, Bart P. F.; Pries, Lotta-Katrin; Have, Margreet ten; Graaf, Ron de; Dorsselaer, Saskia van; Klingenberg, Boris; Os, Jim van; Ioannidis, John P. A.

doi:10.1093/schbul/sby118

Cited by 57 publications

(55 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second, given the sample size and explorative nature of the study, we focused on main and interaction associations of previously established environmental factors and PRS‐SCZ. However, the reality is much more complex than current statistical models can accommodate, involving dynamic interactions, causal and non‐causal associations within the exposome (e.g., dense correlation matrix of environmental factors influenced by the timing, duration, severity and extent of repeated exposures over time); the genome (e.g., epistasis, redundancy and pleiotropy); and the phenome (multidimensional syndromal diversity). Third, instead of the commonly‐exercised selective reporting of one exposure at a time, we embraced a quasi‐systematic approach to provide an overall picture of the gene‐environment interactions findings from this dataset.…”

Section: Discussionmentioning

confidence: 99%

“…We recently discussed the challenges of evaluating the role of environmental exposures in psychiatry and the need to use exposure‐wide systematic approaches to separate genuine strong signals from selective reporting. Guided by this, we aimed to analyze the main and joint associations of environmental exposures and PRS‐SCZ in a cross‐sectional sample that was specifically collected to test for gene‐environment interactions in schizophrenia.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: results from the EUGEI study

et al. 2019

Self Cite

View full text Add to dashboard Cite

Schizophrenia is a heritable complex phenotype associated with a background risk involving multiple common genetic variants of small effect and a multitude of environmental exposures. Early twin and family studies using proxy‐genetic liability measures suggest gene‐environment interaction in the etiology of schizophrenia spectrum disorders, but the molecular evidence is scarce. Here, by analyzing the main and joint associations of polygenic risk score for schizophrenia (PRS‐SCZ) and environmental exposures in 1,699 patients with a diagnosis of schizophrenia spectrum disorders and 1,542 unrelated controls with no lifetime history of a diagnosis of those disorders, we provide further evidence for gene‐environment interaction in schizophrenia. Evidence was found for additive interaction of molecular genetic risk state for schizophrenia (binary mode of PRS‐SCZ above 75% of the control distribution) with the presence of lifetime regular cannabis use and exposure to early‐life adversities (sexual abuse, emotional abuse, emotional neglect, and bullying), but not with the presence of hearing impairment, season of birth (winter birth), and exposure to physical abuse or physical neglect in childhood. The sensitivity analyses replacing the a priori PRS‐SCZ at 75% with alternative cut‐points (50% and 25%) confirmed the additive interaction. Our results suggest that the etiopathogenesis of schizophrenia involves genetic underpinnings that act by making individuals more sensitive to the effects of some environmental exposures.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: results from the EUGEI study

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the same way that genomic approaches provide significant advantage over candidate gene approaches to understanding the complex genetic architecture of psychiatric disorders, exposomic approaches can deepen our knowledge of the multiple, interactive and time-dependent nongenetic factors that affect risk and resilience for these disorders. While many measurement and analytic challenges remain, meaningful preparatory steps can be taken to ensure that psychiatric cohorts are poised to capitalize on advances in exposomics [188][189][190]. Moreover, collaborative efforts between psychiatric and environmental health researchers would provide an excellent testbed for addressing the integration of different aspects of the external exposome (e.g., environmental chemicals that are the focus of environmental health science studies and larger social and economic environments that are often considered in psychiatric research).…”

Section: Addressing Key Challengesmentioning

confidence: 99%

Beyond the looking glass: recent advances in understanding the impact of environmental exposures on neuropsychiatric disease

Hollander

Cory‐Slechta

Jacka

et al. 2020

Neuropsychopharmacol.

View full text Add to dashboard Cite

The etiologic pathways leading to neuropsychiatric diseases remain poorly defined. As genomic technologies have advanced over the past several decades, considerable progress has been made linking neuropsychiatric disorders to genetic underpinnings. Interest and consideration of nongenetic risk factors (e.g., lead exposure and schizophrenia) have, in contrast, lagged behind heritable frameworks of explanation. Thus, the association of neuropsychiatric illness to environmental chemical exposure, and their potential interactions with genetic susceptibility, are largely unexplored. In this review, we describe emerging approaches for considering the impact of chemical risk factors acting alone and in concert with genetic risk, and point to the potential role of epigenetics in mediating exposure effects on transcription of genes implicated in mental disorders. We highlight recent examples of research in nongenetic risk factors in psychiatric disorders that point to potential shared biological mechanisms-synaptic dysfunction, immune alterations, and gut-brain interactions. We outline new tools and resources that can be harnessed for the study of environmental factors in psychiatric disorders. These tools, combined with emerging experimental evidence, suggest that there is a need to broadly incorporate environmental exposures in psychiatric research, with the ultimate goal of identifying modifiable risk factors and informing new treatment strategies for neuropsychiatric disease.

show abstract

“…Therefore, it is plausible to conceptualize that the sensitivity to daily-life stressors is molded by previous exposure to significant life stressors as discussed in the models of diathesis-stress (14) and sensory processing sensitivity (58). Furthermore, the exposome, a dense network of environmental exposures (59,60), may contribute to a person's sensitivity to stress.…”

Section: Stress Exposure and Emotional Processesmentioning

confidence: 99%

Interaction between polygenic liability for schizophrenia and childhood adversity influences daily-life emotional dysregulation and psychosis proneness

Pries

Klingenberg

Menne-Lothmann

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

AbstractBackgroundThe earliest stages of the pluripotent psychopathology on the pathway to psychotic disorders is represented by emotional dysregulation and subtle psychosis expression, which can be measured using the Ecological Momentary Assessment (EMA). However, it is not clear to what degree common genetic and environmental risk factors for psychosis contribute to variation in these early expressions of psychopathology.MethodsIn this largest ever EMA study of a general population twin cohort including 593 adolescents and young adults between the ages of 15 and 35 years, we tested whether polygenic risk score for schizophrenia (PRS-S) interacts with childhood adversity (the Childhood Trauma Questionnaire score) and daily-life stressors to influence momentary mental state domains (negative affect, positive affect, and subtle psychosis expression) and stress-sensitivity measures.ResultsBoth childhood adversity and daily-life stressors were associated with increased negative affect, decreased positive affect, and increased subtle psychosis expression, while PRS-S was only associated with increased positive affect. No gene–environment correlation was detected. We have provided novel evidence for interaction effects between PRS-S and childhood adversity to influence momentary mental states [negative affect (b = 0.07, 95% CI 0.01 to 0.13, P = 0.013), positive affect (b = −0.05, 95% CI −0.10 to −0.00, P = 0.043), and subtle psychosis expression (b = 0.11, 95% CI 0.03 to 0.19, P = 0.007)] and stress-sensitivity measures.ConclusionExposure to childhood adversities, particularly in individuals with high PRS-S, is pleiotropically associated with emotional dysregulation and psychosis proneness.

show abstract

The Complexities of Evaluating the Exposome in Psychiatry: A Data-Driven Illustration of Challenges and Some Propositions for Amendments

Cited by 57 publications

References 27 publications

Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: results from the EUGEI study

Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: results from the EUGEI study

Beyond the looking glass: recent advances in understanding the impact of environmental exposures on neuropsychiatric disease

Interaction between polygenic liability for schizophrenia and childhood adversity influences daily-life emotional dysregulation and psychosis proneness

Contact Info

Product

Resources

About